INVESTIGADORES
MERESMAN Gabriela Fabiana
congresos y reuniones científicas
Título:
New natural therapies assessment for the treatment of endometriosis.
Autor/es:
RICCI A; OLIVARES C; BILOTAS M; MERESMAN G; BARAÑAO RI
Lugar:
Montpellier
Reunión:
Congreso; 11th World Endometriosis Congress; 2011
Institución organizadora:
World Endometriosis Society
Resumen:
Endometriosis
(EDT) is one of the most common gynecological diseases in women of
reproductive age. Medical therapies are aimed at down-regulating the
ovarian estrogen production using GnRH agonists, progestins,
androgenic agents or oral contraceptives. However, side effects limit
their long-term use. Objective: The aim of this work was to evaluate the effect of 2 natural compounds in vivo,
in a murine model of EDT: epigallocatechin 3-gallate (EGCG), which
constitutes approximately 60% of the catechins in green tea, and
resveratrol (Res), a phytoalexin found naturally in grapes, peanuts,
blueberries and many other plants. Both polyphenols has been related to
antiangiogenic, antioxidant and antiinflammatory effects. Methods:
EDT was surgically induced to 60 female BALB/c mice of 2 months age.
After 15 days, 10 animals were randomly assigned per group and
treatments were initiated: Res I (10mg/kg); Res II (25mg/kg); Control
(Res vehicle); EGCG I (20mg/kg); EGCG II (100mg/kg); Control (EGCG
vehicle). Res was administered daily by intraperitoneal injection and
EGCG by esophageal gavage. After 1 month of treatment, animals were
sacrificed by cervical dislocation. Then peritoneal fluid was collected
and endometrioric-like lesions were counted, measured and removed.
Paraffin sections were used to assess apoptosis and cellular
proliferation levels by Terminal Deoxynucleotidil Transferase-Mediated
dUTP Nick End Labeling (TUNEL) and immunohistochemistry for
Proliferating Cell Nuclear Antigen (PCNA) respectively. Vascular
endothelial growth factor (VEGF) levels were evaluated in the
peritoneal fluid by enzyme-linked immunoassay (ELISA). Statistical
comparisons were performed using KruskalWallis nonparametric analysis
of variance test and Dunns multiple comparison post-test. Results:
Both doses of EGCG were able to reduced the number of developed
lesions (p<0.05) and their size (I p<0.05 and II p<0.01 vs.
Control). However, only Res II reduced lesions size (p<0.01 vs.
Control). The number of established lesions observed per mouse was not
affected by Res treatment. On the other hand, EGCG and Res caused a
similar significant reduction of PCNA positive cells (I p<0.05 and
II p<0.01 vs. Controls), whereas TUNEL positive cells were
increased with both EGCG doses (I p<0.05 and II p<0.01 vs.
Control) but only with Res II (p<0.01 vs. Control). Furthermore,
it has been shown that EGCG reduced peritoneal VEGF levels (I
p<0.001 and II p<0.05 vs. Control) unlike to Res which
increased it (I p<0.001 and p<0.01 vs. Control). Conclusions:
Our data suggest that Res and EGCG have an inhibitory effect on
endometriotic-like lesions development by reducing proliferative levels
and increasing the apoptotic ones. It is important to observe that
treatments which begin the 15th day post-surgery have the
purpose of evaluating their effect on the development of the already
established lesions and not punctually on their establishment. However,
the power of a treatment could be reflected on the total reduction
of the size and therefore have an effect on the mean of the number of
established lesions. These findings are promising and support
further investigation of these compounds as novel strategies for
treating EDT. Besides, the fact to confirm beneficial effects in EDT
by these 2 polyphenols would support the chance to provide natural
compounds to patients in long-term treatment.